Functional characterization of new mutations in Wilson disease gene (ATP7B) using the yeast model


Papur O. S. , Terzioglu O., Koc A.

JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, cilt.31, ss.33-36, 2015 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 31
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1016/j.jtemb.2015.02.006
  • Dergi Adı: JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
  • Sayfa Sayıları: ss.33-36

Özet

The Wilson disease gene, a copper transporting ATPase (Atp7b), is responsible for the sequestration of Cu into secretory vesicles, and this function is exhibited by the orthologous Ccc2p in the yeast. In this study, we aimed to characterize clinically relevant new mutations of human ATP7B (p.T788I, p.V10361 and p.R1038G-fsX83) in yeast lacking the CCC2 gene. Expression of human wild type ATP7B gene in ccc2 Delta, mutant yeast restored the growth deficiency and copper transport activity; however, expression of the mutant forms did not restore the copper transport functions and only partially supported the cell growth. Our data support that p.T788I, p.V1036I and p.R1038G-fsX83 mutations cause functional deficiency in ATP7B functions and suggest that these residues are important for normal ATP7B function. (C) 2015 Elsevier GmbH. All rights reserved.